Related Papers
Toxicity of Ruthenium Complexes in Tumour Cell Lines
Philip Böhler
Ruthenium complexes have gained increasing significance as possible anti-cancer agents during the past few years. Promising characteristics such as decreased side effects and lack of cross-resistance with platinum-based chemotherapeutics such as cisplatin, and recent events such as the successful phase I clinical trial of the ruthenium complex NAMI-A (New Anti-tumour Metastasis Inhibitor A) have shown that ruthenium complexes might prove as additions or alternatives to established organometallic anti-cancer drugs [1]. We investigated five novel ruthenium(II) organometall complexes as well as the well-known compound [(p-cymene)Ru(ethylendiamine)Cl]Cl, all of which are structurally related to ONCO 4417 ([(biphenyl)Ru(ethylendiamine)Cl]Cl), which exhibits cytotoxicity levels comparable to cisplatin in vitro. All complexes were analysed in regard to their cytotoxicity, induction of apoptosis and mechanism of action in different mammalian tumour cell lines. While of the six substances tested, the five novel complexes were found to be essentially non-toxic, [(p-cymene)Ru(ethylendiamine)Cl]Cl was found to exhibit high toxicity in the rat hepatoma cell line H4IIE (EC50 = 3 µM) and moderate toxicity in the human ovarian cancer cell line A2780 (EC50 = 71 µM). Additionally, well-known markers of apoptosis such as caspase 3 activation and DNA fragmentation were examined. Here we report that induction of apoptosis is at least in parts responsible for the cytotoxicity exhibited by the complex, with levels of induction as low as 1 µM as shown by DNA ladder formation. In conclusion, it was shown that, depending on their structural characteristics, novel ruthenium complexes have the potential to become new and potent anti-cancer agents.
Age-dependent modulation of xenobiotic metabolism in primary human skin fibroblasts
Julia Tigges
In no other part of the human body, aging processes are displayed as explicitly as in the skin, but are still far from being fully understood. In addition to that and in contrast to other organs such as liver, there are still gaps regarding our knowledge on the xenobiotic detoxification capacities of human skin, even though skin represents our largest organ and is a very important target for a vast number of potentially harmful chemicals. In our present work we therefore aimed to elucidate the effects of intrinsic aging on xenobiotic detoxification in human skin. We were interested to find out whether and how detoxification capacities change in correlation with age and whether this might lead to a decreased protective potential in the elderly population. We focused on prominent enzymes which were also the objective of previous publications (1,2). To address the above mentioned questions, we used cells from a skin fibroblast culture bank established in our institute containing primar...
Naunyn-Schmiedeberg's Archives of Pharmacology
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V
2013 •
Dr. Petra Weissgerber
EMBO reports
Ion channels in health and disease
2001 •
Markus Hoth, Barbara A Niemeyer, Barbara Niemeyer
Cardiac overexpression of the human 5-HT4 receptor in mice
2010 •
Ulrich Gergs
The Journal of pharmacology and experimental therapeutics
Sildenafil Does Not Prevent Heart Hypertrophy and Fibrosis Induced by Cardiomyocyte Angiotensin II Type 1 Receptor Signaling
2015 •
Hariharan Subramanian
Analyses of several mouse models imply that the phosphodiesterase 5 (PDE5) inhibitor sildenafil (SIL), via increasing cGMP, affords protection against angiotensin II (Ang II)-stimulated cardiac remodeling. However, it is unclear which cell types are involved in these beneficial effects, because Ang II may exert its adverse effects by modulating multiple renovascular and cardiac functions via Ang II type 1 receptors (AT1Rs). To test the hypothesis that SIL/cGMP inhibit cardiac stress provoked by amplified Ang II/AT1R directly in cardiomyocytes (CMs), we studied transgenic mice with CM-specific overexpression of the AT1R under the control of the α-myosin heavy chain promoter (αMHC-AT1R(tg/+)). The extent of cardiac growth was assessed in the absence or presence of SIL and defined by referring changes in heart weight to body weight or tibia length. Hypertrophic marker genes, extracellular matrix-regulating factors, and expression patterns of fibrosis markers were examined in αMHC-AT1R(...
International Journal of Cardiology
Modulation of cardiac contractility by serine/threonine protein phosphatase type 5
2012 •
Ulrich Gergs
Purinergic Signalling
Regulation of TrkB receptor translocation to lipid rafts by adenosine A2A receptors and its functional implications for BDNF-induced regulation of synaptic plasticity
2013 •
Daniela - Pereira
Cell Communication and Signaling
Signal transduction, receptors, mediators and genes: younger than ever - the 13th meeting of the Signal Transduction Society focused on aging and immunology
2010 •
Ria Baumgrass
American Journal of Physiology-Heart and Circulatory Physiology
Modulation of SRCa2+release by the triadin-to-calsequestrin ratio in ventricular myocytes
2012 •
Uwe Kirchhefer
Calsequestrin (CSQ) is a Ca2+storage protein that interacts with triadin (TRN), the ryanodine receptor (RyR), and junctin (JUN) to form a macromolecular tetrameric Ca2+signaling complex in the cardiac junctional sarcoplasmic reticulum (SR). Heart-specific overexpression of CSQ in transgenic mice (TGCSQ) was associated with heart failure, attenuation of SR Ca2+release, and downregulation of associated junctional SR proteins, e.g., TRN. Hence, we tested whether co-overexpression of CSQ and TRN in mouse hearts (TGCxT) could be beneficial for impaired intracellular Ca2+signaling and contractile function. Indeed, the depressed intracellular Ca2+concentration ([Ca]i) peak amplitude in TGCSQwas normalized by co-overexpression in TGCxTmyocytes. This effect was associated with changes in the expression of cardiac Ca2+regulatory proteins. For example, the protein level of the L-type Ca2+channel Cav1.2 was higher in TGCxTcompared with TGCSQ. Sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a...
